PB2232: A RANDOMIZED, CONTROLLED CLINICAL TRIAL (PHASE 2B) OF NS-018 VERSUS BEST AVAILABLE THERAPY IN SUBJECTS WITH PRIMARY OR SECONDARY MYELOFIBROSIS WITH SEVERE THROMBOCYTOPENIA
Authors: Melisa Palacio, Srdan Verstovsek, Tomonori Uno, Taishi Yamashita
Journal: HemaSphere (2023)

Topic: 16. Myeloproliferative neoplasms - Clinical Background: Myelofibrosis (MF) is a life-threatening myeloproliferative neoplasm (MPN) characterized by bone marrow fibrosis, anemia, progressive splenomegaly, and constitutional symptoms. Patients with severe thrombocytopenia (platelets <50,000/μL) have the highest rates of anemia, transfusion dependency, and shortest survival. Treatment options for patients with MF and severe thrombocytopenia are limited due to the high incidence of treatment-related thrombocytopenia using currently available JAK inhibitors for MF. NS-018 (ilginatinib) is a new potent and specific Janus kinase 2 (JAK2) inhibitor which was discovered, designed and synthesized by Nippon Shinyaku Co., Ltd. NS-018 is being developed as a therapeutic agent for MPN including MF. A Phase 1/ 2, multicenter, dose-escalation, open-label study of NS-018 was conducted in subjects with MF (Study No. NS-018-101 [NCT01423851]). Aims: To evaluate the efficacy and safety of NS-018 300 mg twice daily (BID) vs best available therapy (BAT) in patients with MF and severe thrombocytopenia, the NS-018-201 study (NCT04854096) was designed. Methods: NS-018-201 study is a multinational, multicenter, randomized, controlled phase 2b trial of NS-018 vs BAT patients with primary or secondary MF with DIPSS intermediate-2 or high-risk disease, ECOG performance status 0-2, platelet counts <50,000/μL, naive or prior JAK2 inhibitor therapy (up to 180 days). Subjects will be stratified at baseline by spleen volume and by history of prior JAK inhibitor treatment, and randomized to receive either NS-018 (300mg twice a daily) or BAT (control group). The stratification factors will be as follows: 1) spleen volume (≥2000 cm3 versus <2000 cm3); 2) JAK inhibitor (naive versus prior treatment). There will be no MF-directed treatment (other than JAK inhibitor) for at least 2 weeks prior to initiation of NS-018 or BAT. A total of 120 subjects are expected to be enrolled and randomized 1:1 to either NS-018 or BAT (may include hydroxyurea, danazol, fedratinib, ruxolitinib, or no therapy). The co-primary endpoints are the proportion of patients achieving a ≥35% SVR and the proportion achieving a ≥50% reduction in modified TSS from baseline at week 24. Secondary endpoint is safety. Exploratory endpoints include fatigue improvement (based on PROMIS Fatigue - Short Form 7b), hematologic improvement, IWG-MRT response criteria, changes in biomarkers and gene expression. NS-018-201 study is currently enrolling at sites worldwide. Results: A Randomized, Controlled Clinical Trial (phase 2b) of NS-018 versus Best Available Therapy in Subjects with Primary or Secondary MF with Severe Thrombocytopenia was designed. Summary/Conclusion: NS-018-201 study is currently enrolling at sites worldwide. Co-primary endpoints of reduction of spleen size and symptomatic scores, as well as safety will be elucidated. Other exploratory endpoints which will benefit to understand and manage the disease are also investigated. Keywords: Myelofibrosis, Janus Kinase inhibitor, Thrombocytopenia